Therapeutic drug monitoring of linezolid in Chinese premature neonates: a population pharmacokinetic analysis and dosage optimization.

This study aimed to develop a pharmacokinetic model of linezolid in premature neonates and evaluate and optimize the administration regimen. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to detect the blood concentration data of 54 premature neonates after intravenous administration of linezolid, and the relevant clinical data were collected. The population pharmacokinetic (PPK) model was established by nonlinear mixed effects modeling. Based on the final model parameters, the optimal administration regimen of linezolid in premature neonates with different body surface areas (BSA) was simulated and evaluated. The pharmacokinetic properties of linezolid in premature neonates are best described by a single-compartment model with primary elimination. The population typical values for apparent volume of distribution and clearance were 0.783 L and 0.154 L/h, respectively. BSA was a statistically significant covariate with clearance (CL) and volume of distribution (Vd). Monte Carlo simulations showed that the optimal administration regimen for linezolid in premature neonates was 6 mg/kg q8h for BSA 0.11 m2, 7 mg/kg q8h for BSA 0.13 m2, and 9 mg/kg q8h for BSA 0.15 m2 with minimum inhibitory concentration (MIC) ≤1 mg/L, 7 mg/kg q8h for BSA 0.11 m2, 8 mg/kg q8h for BSA 0.13 m2, and 10 mg/kg q8h for BSA 0.15 m2 with MIC = 2 mg/L. A pharmacokinetic model was developed to predict the blood concentration on linezolid in premature neonates. Based on this model, the optimal administration regimen of linezolid in premature neonates needs to be individualized according to different BSA levels.

Receptor-interacting protein kinase-3 (RIPK3): a new biomarker for necrotising enterocolitis in preterm infants.

OBJECTIVE: This study aimed to evaluate the role of receptor-interacting protein kinase-3 (RIPK3) in the diagnosis, estimation of disease severity, and prognosis of premature infants with necrotising enterocolitis (NEC). METHODS: RIPK3, lactic acid (LA), and C-reactive protein (CRP) levels were measured in the peripheral blood of 108 premature infants between 2019 and 2023, including 24 with stage II NEC, 18 with stage III NEC and 66 controls. Diagnostic values of the indicators for NEC were evaluated via receiver operating characteristic (ROC) curve analysis. RESULTS: Plasma RIPK3 and LA levels upon NEC suspicion in neonates with stage III NEC were 32.37 ± 16.20 ng/mL. The ROC curve for the combination of RIPK3, LA, CRP for NEC diagnosis were 0.925. The time to full enteral feeding (FEFt) after recovery from NEC was different between two expression groups of plasma RIPK3 (RIPK3 < 20.06 ng/mL and RIPK3 ≥ 20.06 ng/mL). CONCLUSION: Plasma RIPK3 can be used as a promising marker for the diagnosis and estimation of disease severity of premature infants with NEC and for the guidance on proper feeding strategies after recovery from NEC.

A real-world cost-effectiveness study of vancomycin versus linezolid for the treatment of late-onset neonatal sepsis in the NICU in China.

BACKGROUND AND OBJECTIVE: Currently, the detection rates of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCoNS) in the blood cultures of neonates with sepsis exceed the national average drug resistance level, and vancomycin and linezolid are the primary antibacterial drugs used for these resistant bacteria according to the results of etiological examinations. However, a comprehensive evaluation of their costs and benefits in late-onset neonatal sepsis in a neonatal intensive care unit (NICU) has not been conducted. This study aimed to compare the cost and effectiveness of vancomycin and linezolid in treating neonatal sepsis in the NICU. METHODS: A cost-effectiveness analysis of real-world data was carried out by retrospective study in our hospital, and the cost and effectiveness of vancomycin and linezolid were compared by establishing a decision tree model. The drug doses in the model were 0.6 g for linezolid and 0.5 g for vancomycin. The cost break down included cost of medical ward, NICU stay, intravenous infusion of vancomycin or linezolid, all monitoring tests, culture tests and drugs. The unit costs were sourced from hospital information systems. The effectiveness rates were obtained by cumulative probability analysis. One-way sensitivity analysis was used to analyze uncertain influencing factors. RESULTS: The effectiveness rates of vancomycin and linezolid in treating neonatal sepsis in the NICU were 89.74% and 90.14%, respectively, with no significant difference. The average cost in the vancomycin group was ¥12261.43, and the average cost in the linezolid group was ¥17227.96. The incremental cost effectiveness was ¥12416.33 cost per additional neonate with treatment success in the linezolid group compared to vancomycin group at discharge. Factors that had the greatest influence on the sensitivity of the incremental cost-effectiveness ratio were the price of linezolid and the effectiveness rates. CONCLUSIONS: The cost for treatment success of one neonate in linezolid group was ¥5449.17 more than that in vancomycin group, indicating that vancomycin was more cost-effective. Therefore, these results can provide a reference for a cost effectiveness treatment scheme for neonatal sepsis in the NICU.

Incidence of extrauterine growth retardation and its risk factors in very preterm infants during hospitalization: a multicenter prospective study. / ä½é™¢æžæ—©äº§å„¿å®«å¤–ç”Ÿé•¿è¿Ÿç¼“åŠç›¸å ³å› ç´ çš„å¤šä¸­å¿ƒå‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS: It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.

The potential value of plasma receptor interacting protein 3 in neonates with culture-positive late-onset sepsis.

BACKGROUND: Late-onset sepsis (LOS) is a systemic inflammatory response syndrome in neonates, and the molecular mechanism of LOS is incompletely characterized. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in LOS. METHODS: 63 neonates with LOS supported by positive culture and 79 neonates without sepsis were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with the whole blood hypersensitive C-reactive protein (hs-CRP) level and platelet count (PLT). Differences in RIP3, hs-CRP and PLT between the two groups were compared. Changes in the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for LOS was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: In the sepsis group, RIP3 and hs-CRP levels were significantly higher than those in the control group (RIP3, p < 0.0001; hs-CRP, p < 0.0001), and PLT was significantly lower than that in the control group (p < 0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors were significantly decreased (p < 0.0001) and PLT significantly improved (p = 0.0216). With RIP3 > 15,845.19 pg/mL, hs-CRP > 5.00 mg/L, and PLT < 204.00 × 109/L as the positive criteria, the sensitivity values of the three indicators in the diagnosis of LOS were 69.8%, 60.3%, 60.3%, respectively, and the specificity values were 92.4%, 96.2%, 79.8%, respectively. The combination of RIP3, hs-CRP and PLT had a sensitivity of 77.8% and specificity of 97.5%. CONCLUSIONS: RIP3 may contribute to the early diagnosis of LOS and monitoring of treatment effect. The combined detection of RIP3, hs-CRP and PLT may be more effective than individual detection in the diagnosis of LOS.

Significance of sTREM-1 in early prediction of ventilator-associated pneumonia in neonates: a single-center, prospective, observational study.

BACKGROUND: To evaluate whether soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) can be used as an early predictor of ventilator-associated pneumonia (VAP). METHODS: Ventilated neonatal patients admitted into the neonatology department between January 2017 and January 2018 were divided into VAP (n = 30) and non-VAP (n = 30) groups. Serum sTREM, procalcitonin (PCT), C-reactive protein and interleukin-6 levels were measured at 0, 24, 72, and 120 h after initiation of mechanical ventilation (MV). Correlations between blood biomarker concentrations and VAP occurrence were analyzed. Predictive factors for VAP were identified by logistic regression analysis and Hosmer-Lemeshow test, and the predictive value of sTREM-1 and biomarker combinations for VAP was determined by receiver operating characteristic curve analysis. RESULTS: The serum sTREM-1 concentration was significantly higher in the VAP group than in the non-VAP group after 72 and 120 h of MV (72 h: 289.5 (179.6-427.0) vs 202.9 (154.8-279.6) pg/ml, P < 0.001; 120 h: 183.9 (119.8-232.1) vs 141.3 (99.8-179.1) pg/ml, P = 0.042). The area under the curve (AUC) for sTREM-1 at 72 h was 0.902 with a sensitivity of 90% and specificity of 77% for the optimal cut-off value of 165.05 pg/ml. Addition of PCT to sTERM-1 at 72 h further improved the predictive value, with this combination having an AUC of 0.971 (95% confidence interval: 0.938-1.000), sensitivity of 0.96, specificity of 0.88, and Youden index of 0.84. CONCLUSION: sTREM-1 is a reliable predictor of VAP in neonates, and combined measurement of serum levels of sTREM-1 and PCT after 72 h of MV provided the most accurate prediction of VAP in neonatal patients.

[Safety and efficacy of caffeine use started at different time in preterm infants: a multicenter study in Jiangsu Province, China].

OBJECTIVE: To study the efficacy and safety of caffeine used in the early (≤72 hours after birth) and late (>72 hours after birth) stage in preterm infants with a gestational age of ≤31 weeks. METHODS: A retrospective analysis was performed for 640 preterm infants (with a gestational age of ≤31 weeks) who were admitted to the neonatal intensive care unit of eight hospitals in Jiangsu Province, China. Of the 640 preterm infants, 510 were given caffeine in the early stage (≤72 hours after birth; early use group) and 130 were given caffeine in the late stage (>72 hours after birth; late use group). The clinical data were compared between the two groups. RESULTS: There were no significant differences in birth weight, Apgar score, sex, gestational age, and age on admission between the two groups (P>0.05). Compared with the late use group, the early use group had a significantly younger age at the beginning and withdrawal of caffeine treatment (P<0.05) and a significantly shorter duration of caffeine treatment (P<0.05). There was no significant difference in respiratory support on admission between the two groups (P>0.05). Compared with the late use group, the early use group had significantly lower incidence rate of apnea (P<0.05) and significantly shorter oxygen supply time and length of hospital stay (P<0.05). There were no significant differences between the two groups in the incidence rates of neonatal intracranial hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, retinopathy of prematurity, and patent ductus arteriosus at discharge and NBNA score at the corrected gestational age of 40 weeks (P>0.05). However, significant differences were found in the incidence of bronchopulmonary dysplasia and the rate of home oxygen therapy, but there was no significant difference in the mortality rate between the two groups (P>0.05). CONCLUSIONS: Early use of caffeine can shorten the duration of caffeine treatment, oxygen supply time, and length of hospital stay, with little adverse effect, in preterm infants with a gestational age of ≤31 weeks.

[Clinical efficacy of heated humidified high-flow nasal cannula in preventing extubation failure in neonates: a Meta analysis].

OBJECTIVE: To evaluate the efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) in preventing extubation failure in neonates. METHODS: A literature search was performed using PubMed, Cochrane Library, FMRS, and CNKI to collect the randomized controlled trials (RCTs) and quasi-RCTs which compared the clinical efficacy of HHHFNC and nasal continuous positive airway pressure (NCPAP) in preventing extubation failure in neonates. The identified studies were finally selected after full-text search and quality assessment and then subjected to a Meta analysis using RevMan 5.3. RESULTS: Five eligible trials involving 1040 neonates were included in the Meta analysis. The Meta analysis showed that there was no significant difference in treatment failure rate between the HHHFNC and the NCPAP groups. The HHHFNC group had significantly lower incidence rates of nasal trauma (OR=0.49, 95% CI: 0.34-0.71, P=0.0001) and pneumothorax (OR=0.27, 95% CI: 0.07-0.97, P=0.04) than the NCPAP group, but there were no significant differences in the duration to reach full oral feedings and the incidence rates of serious adverse events or other complications between the two groups, such as in-hospital mortality, bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity. CONCLUSIONS: HHHFNC is safe and effective in preventing extubation failure in neonates.

A nomogram to predict the risk of death during hospitalization in Chinese neonates with respiratory failure.

Background: Neonatal respiratory failure (NRF) is a critical condition with high morbidity and mortality rates. This study aimed to develop a nomogram prediction model to early predict the risk of death in Chinese neonates with NRF. Methods: A retrospective analysis was conducted on NRF neonates from 21 tertiary neonatal intensive care units (NICUs) across 13 prefecture-level cities in Jiangsu Province, China, from March 2019 to March 2022. NRF neonates from one random NICU were selected as the external validation set, while those from the remaining 20 NICUs were divided into the training set and the internal validation set at a 7:3 ratio. Death was the primary outcome. LASSO regression and multivariate logistic regression were used to identify the predictive factors from the training set and then the nomogram was constructed. Results: A total of 5387 neonates with NRF were included in the analysis. Among them, 3444 were in the training set, 1470 were in the internal validation set, and 473 were in the external validation set. The nomogram was constructed based on the eight predictors of the 1-min Apgar score, birth weight, gestational age, the relationship between birth weight and gestational age, mode of first respiratory support, inhaled nitric oxide, antenatal corticosteroids, and vasoactive drugs. The area under the curve of the nomogram in the training set, internal validation set, and external validation set was 0.763, 0.733, and 0.891, respectively. The P-values of the Hosmer-Lemeshow goodness of fit test were 0.638, 0.273, and 0.253, respectively. Brier scores were 0.066, 0.072, and 0.037, respectively. The decision curve analysis demonstrated a significant net benefit in all cases. These data indicate the good performance of the nomogram. Conclusions: This nomogram can serve as a reference for clinicians to identify high-risk neonates early and reduce the incidence of neonatal mortality.

The clinical characteristics and risk factors analysis within one week before the onset of necrotizing enterocolitis.

There are considerable researches on risk factors for necrotizing enterocolitis (NEC), focusing primarily on the entire course before onset. However, fewer studies address risk factors within the brief period before NEC occurrence. The current study aims to retrospectively analyze the clinical data of NEC patients while focusing on relevant risk factors in the preceding week of NEC onset. Infants born between January 2019 and December 2021 at Suzhou Municipal Hospital and Suzhou University Children's Hospital with a birth weight < 1500 g or a gestational age < 32 weeks were included. Around 54 NEC patients and 180 controls were recruited in the study. NEC patients satisfying the inclusion criteria formed the case group, while a 1:4 matching principle helped select the control group based on gestational age and birth weight. A statistically significant difference was observed between groups when red blood cell transfusions were compared the week before NEC onset (adjusted OR and 95% CI 2.16 (1.10, 4.24)). Broad-spectrum antibiotic usage before NEC occurrence was significantly lower in the NEC group than in the control group (adjusted OR and 95% CI 0.95 (0.91, 0.99)). A statistically significant difference was observed between groups while comparing patent ductus arteriosus (PDA) (adjusted OR and 95% CI 2.45 (1.23, 4.91)). The indication for packed red blood cell transfusion should be strictly controlled. Moreover, close monitoring of the patient's condition for NEC occurrence should be conducted within one-week post-transfusion. Accurately identifying infections and using broad-spectrum antibiotics can reduce the incidence of NEC.

N-Acetylcysteine Alleviates Necrotizing Enterocolitis by Depressing SESN2 Expression to Inhibit Ferroptosis in Intestinal Epithelial Cells.

Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.

Unexpected decrease in necrotizing enterocolitis morbidity during the COVID-19 pandemic-A single-centre retrospective study.

Background: The impact of the coronavirus disease 2019 (COVID-19) pandemic on neonatal necrotizing enterocolitis (NEC) is not well characterised. This cross-sectional study evaluated the potential effects of pandemic-related measures on NEC morbidity in premature infants in a neonatal ward during the COVID-19 pandemic. Methods: This was a retrospective study conducted in a tertiary neonatal ward in eastern and central China over 6 consecutive years (2017, 2018, 2019, 2020, 2021 and 2022). The medical records of 189 premature infants with stage II or III NEC were reviewed for clinical manifestations and aetiologies. The data were analysed and compared between the prepandemic period (2017, 2018, and 2019) and the pandemic period (2020, 2021 and 2022). Results: A total of 9,903 infants with gestational age (GA) < 37 weeks were enrolled, including 5,382 in the prepandemic period and 4,521 in the pandemic period. A reduction in stage II or III NEC morbidity was observed in infants with GA < 37 weeks, with an average annual morbidity of 2.29% (123/5,382) (95% CI, 1.89%-2.68%) in the prepandemic period and 1.46% (66/4,521) (95% CI, 1.11%-1.81%) in the pandemic period. NEC morbidity showed resurgent characteristics in 2021. When prepandemic coinfections were excluded, most cases of NEC with bloodstream infections in the prepandemic period were attributable to Gram-negative bacteria (27/32, 84.38%), mainly Klebsiella pneumoniae, while in the pandemic period they were attributable to Gram-positive bacteria (10/18, 55.56%), mainly Staphylococcus aureus. Antimicrobial susceptibility testing revealed that Klebsiella pneumoniae was 100% sensitive to meropenem, imipenem, ciprofloxacin and levofloxacin and 100% resistant to ampicillin. Staphylococcus capitis was 100% sensitive to vancomycin, linezolid, tetracycline, cotrimoxazole and cefoxitin and 100% resistant to penicillin and benzathine. Conclusions: COVID-19 pandemic-related interventions can reduce the morbidity of NEC and change the pathogen spectrum in patients with bloodstream infections. We need to understand the exact factors leading to these changes.

Influence of perinatal factors on full-term low-birth-weight infants and construction of a predictive model.

BACKGROUND: Being too light at birth can increase the risk of various diseases during infancy. AIM: To explore the effect of perinatal factors on term low-birth-weight (LBW) infants and build a predictive model. This model aims to guide the clinical management of pregnant women's healthcare during pregnancy and support the healthy growth of newborns. METHODS: A retrospective analysis was conducted on data from 1794 single full-term pregnant women who gave birth. Newborns were grouped based on birth weight: Those with birth weight < 2.5 kg were classified as the low-weight group, and those with birth weight between 2.5 kg and 4 kg were included in the normal group. Multiple logistic regression analysis was used to identify the factors influencing the occurrence of full-term LBW. A risk prediction model was established based on the analysis results. The effectiveness of the model was analyzed using the Hosmer-Leme show test and receiver operating characteristic (ROC) curve to verify the accuracy of the predictions. RESULTS: Among the 1794 pregnant women, there were 62 cases of neonatal weight < 2.5 kg, resulting in an LBW incidence rate of 3.46%. The factors influencing full-term LBW included low maternal education level [odds ratio (OR) = 1.416], fewer prenatal examinations (OR = 2.907), insufficient weight gain during pregnancy (OR = 3.695), irregular calcium supplementation during pregnancy (OR = 1.756), and pregnancy hypertension syndrome (OR = 2.192). The prediction model equation was obtained as follows: Logit (P) = 0.348 × maternal education level + 1.067 × number of prenatal examinations + 1.307 × insufficient weight gain during pregnancy + 0.563 × irregular calcium supplementation during pregnancy + 0.785 × pregnancy hypertension syndrome - 29.164. The area under the ROC curve for this model was 0.853, with a sensitivity of 0.852 and a specificity of 0.821. The Hosmer-Leme show test yielded χ 2 = 2.185, P = 0.449, indicating a good fit. The overall accuracy of the clinical validation model was 81.67%. CONCLUSION: The occurrence of full-term LBW is related to maternal education, the number of prenatal examinations, weight gain during pregnancy, calcium supplementation during pregnancy, and pregnancy-induced hypertension. The constructed predictive model can effectively predict the risk of full-term LBW.

[Application of umbilical venous catheter combined with peripherally inserted central catheter in very low birth weight infants].

OBJECTIVE: To study the application of umbilical venous catheter (UVC) combined with peripherally inserted central catheter (PICC) in very low birth weight infants (VLBWIs). METHODS: A retrospective analysis was performed on the VLBWIs in the neonatal intensive care unit who received UVC combined with PICC (catheter group, n=63) or did not receive the catheter treatment (non-catheter group, n=38) to compare the differences in nosocomial infection, weight gain, and length of hospital stay between the two groups. RESULTS: The rate of nosocomial infection was 17% in the catheter group and 24% in the non-catheter group (P>0.05). Compared with the non-catheter group, the catheter group had a significantly higher weight gain (11.7±2.0 g/kg•d vs 10.6±2.3 g/kg•d; P<0.05) and a significantly shorter length of hospital stay (40±11 days vs 45±14 days; P<0.05). There was no significant difference in the incidence of complications between the two groups. CONCLUSIONS: Compared with those not receiving catheter treatment, the VLBWIs receiving UVC combined with PICC have a markedly higher weight gain and a markedly shorter length of hospital stay and show a declining trend in the rate of nosocomial infection.

Use of antenatal corticosteroids among infants with gestational age at 24 to 31 weeks in 57 neonatal intensive care units of China: a cross-sectional study.

BACKGROUND: Antenatal corticosteroids (ACS) can significantly improve the outcomes of preterm infants. This study aimed to describe the ACS use rates among preterm infants admitted to Chinese neonatal intensive care units (NICU) and to explore perinatal factors associated with ACS use, using the largest contemporary cohort of very preterm infants in China. METHODS: This cross-sectional study enrolled all infants born at 24 +0 to 31 +6 weeks and admitted to 57 NICUs of the Chinese Neonatal Network from January 1st, 2019 to December 30th, 2019. The ACS administration was defined as at least one dose of dexamethasone and betamethasone given before delivery. Multiple logistic regressions were applied to determine the association between perinatal factors and ACS usage. RESULTS: A total of 7828 infants were enrolled, among which 6103 (78.0%) infants received ACS. ACS use rates increased with increasing gestational age (GA), from 177/259 (68.3%) at 24 to 25 weeks' gestation to 3120/3960 (78.8%) at 30 to 31 weeks' gestation. Among infants exposed to ACS, 2999 of 6103 (49.1%) infants received a single complete course, and 33.4% (2039/6103) infants received a partial course. ACS use rates varied from 30.2% to 100% among different hospitals. Multivariate regression showed that increasing GA, born in hospital (inborn), increasing maternal age, maternal hypertension and premature rupture of membranes were associated with higher likelihood to receive ACS. CONCLUSIONS: The use rate of ACS remained low for infants at 24 to 31 weeks' gestation admitted to Chinese NICUs, with fewer infants receiving a complete course. The use rates varied significantly among different hospitals. Efforts are urgently needed to propose improvement measures and thus improve the usage of ACS.

Deep learning-assisted ultra-accurate smartphone testing of paper-based colorimetric ELISA assays.

Smartphone has long been considered as one excellent platform for disease screening and diagnosis, especially when combined with microfluidic paper-based analytical devices (µPADs) that feature low cost, ease of use, and pump-free operations. In this paper, we report a deep learning-assisted smartphone platform for ultra-accurate testing of paper-based microfluidic colorimetric enzyme-linked immunosorbent assay (c-ELISA). Different from existing smartphone-based µPAD platforms, whose sensing reliability is suffered from uncontrolled ambient lighting conditions, our platform is able to eliminate those random lighting influences for enhanced sensing accuracy. We first constructed a dataset that contains c-ELISA results (n = 2048) of rabbit IgG as the model target on µPADs under eight controlled lighting conditions. Those images are then used to train four different mainstream deep learning algorithms. By training with these images, the deep learning algorithms can well eliminate the influences of lighting conditions. Among them, the GoogLeNet algorithm gives the highest accuracy (>97%) in quantitative rabbit IgG concentration classification/prediction, which also provides 4% higher area under curve (AUC) value than that of the traditional curve fitting results analysis method. In addition, we fully automate the whole sensing process and achieve the "image in, answer out" to maximize the convenience of the smartphone. A simple and user-friendly smartphone application has been developed that controls the whole process. This newly developed platform further enhances the sensing performance of µPADs for use by laypersons in low-resource areas and can be facilely adapted to the real disease protein biomarkers detection by c-ELISA on µPADs.

Early Antibiotic Use and Neonatal Outcomes Among Preterm Infants Without Infections.

OBJECTIVES: To determine whether use, duration, and types of early antibiotics were associated with neonatal outcomes and late antibiotic use in preterm infants without infection-related diseases. METHODS: This cohort study enrolled infants admitted to 25 tertiary NICUs in China within 24 hours of birth during 2015-2018. Death, discharge, or infection-related morbidities within 7 days of birth; major congenital anomalies; and error data on antibiotic use were excluded. The composite outcome was death or adverse morbidities. Late antibiotic use indicated antibiotics used after 7 days of age. Late antibiotic use rate was total antibiotic use days divided by the days of hospital stay after the first 7 days of life. RESULTS: Among 21 540 infants, 18 302 (85.0%) received early antibiotics. Early antibiotics was related to increased bronchopulmonary dysplasia (BPD) (adjusted odds ratio [aOR], 1.28; 95% confidence interval [CI], 1.05-1.56), late antibiotic use (aOR, 4.64; 95% CI, 4.19-5.14), and late antibiotic use rate (adjusted mean difference, 130 days/1000 patient-days; 95% CI, 112-147). Each additional day of early antibiotics was associated with increased BPD (aOR, 1.07; 95% CI, 1.04-1.10) and late antibiotic use (aOR, 1.41; 95% CI, 1.39-1.43). Broad-spectrum antibiotics showed larger effect size on neonatal outcomes than narrow-spectrum antibiotics. The correlation between early antibiotics and outcomes was significant among noncritical infants but disappeared for critical infants. CONCLUSIONS: Among infants without infection, early antibiotic use was associated with increased risk of BPD and late antibiotic use. Judicious early antibiotic use, especially avoiding prolonged duration and broad-spectrum antibiotics among noncritical infants, may improve neonatal outcomes and overall antibiotic use in NICUs.

Vancomycin in neonatal sepsis: predictive performance of a Chinese neonatal population pharmacokinetic model and clinical efficacy evaluation.

BACKGROUND: In the neonatal population, individual calculation and adjustment of vancomycin (VCM) doses has been recommended based on population pharmacokinetics (PPK) methods. OBJECTIVE: Our previous study established a Chinese neonatal VCM PPK model. The main goal of this study was to evaluate the predictive performance of this PPK model for VCM trough concentration. METHODS: The data on neonatal severe infection patients treated with VCM were retrospectively collected. The predictive performance of this PPK model was expressed using mean prediction error (MPE), mean absolute prediction error (MAPE), sensitivity and specificity. Linear regression analysis was used to compare predicted and measured VCM concentrations. We drew the receiver operating characteristic (ROC) curve to evaluate the predictive efficacy of the ratio of area under the concentration-time curve over 24 hours to minimum inhibitory concentration (AUC0-24/MIC) and trough concentration for clinical efficacy. RESULTS: A total of 40 neonates with Gram-positive bacterial sepsis were included. After VCM treatment, 32 (80%) neonates were clinically cured. Eight cases were a clinical failure: the trough concentrations and AUC0-24 were lower than that of the clinical cure patients (8.70±4.30 vs 14.30±4.50 mg/L, p=0.003; 404.30±122.80 vs 515.40±131.70, p=0.037). The measured and predicted trough concentration were 11.16 (5.96, 16.53) mg/L and 10.13 (6.61, 15.73) mg/L, respectively. The MPE and MAPE were 4.62% and 13.26% (5.30%, 25.88%), respectively. The proportion of MAPE <30% in the adjusted regimen was higher than the initial regimen (89.66% vs 65.00%, p=0.039). Predictions of sensitivity and specificity by this PPK model were 88.24% and 94.29%, respectively. The coefficients of determination of linear regression analysis were 0.9171 and 0.9009 for the initial and adjusted regimen, respectively. The AUC0-24 was correlated with the trough concentration (r=0.587, p<0.001). The ROC curve indicated that the optimal cut-off points for predicting clinical efficacy were AUC0-24/MIC >425.47 and trough concentration >9.45 mg/L. CONCLUSION: This PPK model has good predictive performance in Chinese neonatal patients. Both AUC0-24/MIC and trough concentration can predict the clinical efficacy of antibacterial treatment.

A Regression Model to Predict Linezolid Induced Thrombocytopenia in Neonatal Sepsis Patients: A Ten-Year Retrospective Cohort Study.

Background: Linezolid-induced thrombocytopenia (LIT) is the main factor limiting the clinical application of linezolid (LZD). The incidence and risk factors of LIT in neonatal patients were possibly different from other populations based on pathophysiological characteristics. The purpose of this study was to establish a regression model for predicting LIT in neonatal sepsis patients. Methods: We retrospectively included 518 patients and divided them into the LIT group and the non-LIT group. A logistic regression analysis was used to analyze the factors related to LIT, and a regression model was established. A receiver operating characteristic (ROC) curve was drawn to evaluate the model's predictive value. We prospectively collected 39 patients' data to validate the model and evaluate the effect of LZD pharmacokinetics on LIT. Results: Among the 518 patients, 103 patients (19.9%) developed LIT. The Kaplan-Meier plot revealed that the overall median time from the initiation of LZD treatment to the onset of LIT in preterm infants was much shorter when compared with term infants [10 (6, 12) vs. 13 (9.75, 16.5), p = 0.004]. Multiple logistic regression analysis indicated that the independent risk factors of LIT were lower weight at medication, younger gestational ages, late-onset sepsis, necrotizing enterocolitis, mechanical ventilation, longer durations of LZD treatment, and lower baseline of platelet level. We established the above seven-variable prediction regression model and calculated the predictive probability. The ROC curve showed that the predicted probability of combined body weight, gestational age, duration of LZD treatment, and baseline of platelet had better sensitivity (84.4%), specificity (74.2%), and maximum AUC (AUC = 0.873). LIT occurred in 9 out of 39 patients (23.1%), and the accuracies of positive and negative predictions of LIT were 88.9 and 76.7%, respectively. Compared with the non-LIT patients, the LIT patients had higher trough concentration [11.49 (6.86, 15.13) vs. 5.51 (2.80, 11.61) mg/L; p = 0.028] but lower apparent volume of distribution (Vd) [0.778 (0.687, 1.421) vs. 1.322 (1.099, 1.610) L; p = 0.010]. Conclusion: The incidence of LIT was high in neonatal sepsis patients, especially in preterm infants. LIT occurred earlier in preterm infants than in term infants. The regression model of seven variables had a high predictive value for predicting LIT. LIT was correlated with higher trough concentration and lower Vd.

The development and validation of a predictive model for neonatal phototherapy outcome using admission indicators.

Delayed exchange transfusion therapy (ETT) after phototherapy failure for newborns with severe hyperbilirubinemia could lead to serious complications such as bilirubin encephalopathy (BE). In this current manuscript we developed and validated a model using admission data for early prediction of phototherapy failure. We retrospectively examined the medical records of 292 newborns with severe hyperbilirubinemia as the training cohort and another 52 neonates as the validation cohort. Logistic regression modeling was employed to create a predictive model with seven significant admission indicators, i.e., age, past medical history, presence of hemolysis, hemoglobin, neutrophil proportion, albumin (ALB), and total serum bilirubin (TSB). To validate the model, two other models with conventional indicators were created, one incorporating the admission indicators and phototherapy failure outcome and the other using TSB decrease after phototherapy failure as a variable and phototherapy outcome as an outcome indicator. The area under the curve (AUC) of the predictive model was 0.958 [95% confidence interval (CI): 0.924-0.993] and 0.961 (95% CI: 0.914-1.000) in the training and validation cohorts, respectively. Compared with the conventional models, the new model had better predictive power and greater value for clinical decision-making by providing a possibly earlier and more accurate prediction of phototherapy failure. More rapid clinical decision-making and interventions may potentially minimize occurrence of serious complications of severe neonatal hyperbilirubinemia.